Fibroblast growth factors are polypeptides expressed in developing and adult tissues. They are involved in several physiological mechanisms including for example metabolic regulation and cellular differentiation. A whole family of more than twenty fibroblast growth factors exists (the FGF family). Three members of the FGF family including FGF19, FGF21, and FGF23 form a subfamily functioning as endocrine factors involved in metabolic regulation.
Fibroblast Growth Factor 21 or FGF-21, herein for short FGF21, is expressed preferentially in the liver and has been shown to exert hormone-like metabolic effects.
In decades, it has been possible to prepare a large range of peptides and proteins recombinantly, for example in a bacterium such as Eschericia Coli or in yeast such as Saccharomyces cerevisiae. Proteins expressed in yeast are often O-glycosylated. In pharmaceutical proteins, O-glycosylation should usually be avoided. For example, human FGF21 is highly O-glycosylated when prepared recombinantly in yeast.
Claim 1 in US 2002/0068325 relates to a method of producing a heterologous protein in fungi comprising: providing a recipient fungi cell wherein the quality control mechanism in said cell is modified so that incompletely folded heterologous proteins are not degraded in the endoplasmic reticulum; and introducing to said recipient fungi cell a polynucleotide expression construct. According to claim 8 therein, the recipient cell is modified in the mannosyltransferase gene comprising a gene selected from the group consisting of PMT1, PMT2, PMT3, PMT4, PMT5 and PMT6. FGF is not dealt with in said US patent application.